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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02477800




Registration number
NCT02477800
Ethics application status
Date submitted
18/06/2015
Date registered
23/06/2015
Date last updated
2/09/2021

Titles & IDs
Public title
221AD301 Phase 3 Study of Aducanumab (BIIB037) in Early Alzheimer's Disease
Scientific title
A Phase 3 Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of Aducanumab (BIIB037) in Subjects With Early Alzheimer's Disease
Secondary ID [1] 0 0
2015-000966-72
Secondary ID [2] 0 0
221AD301
Universal Trial Number (UTN)
Trial acronym
ENGAGE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Alzheimer's Disease 0 0
Condition category
Condition code
Neurological 0 0 0 0
Alzheimer's disease
Neurological 0 0 0 0
Dementias

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Aducanumab (BIIB037)
Treatment: Drugs - Aducanumab (BIIB037)
Treatment: Drugs - Placebo

Experimental: Low Dose - Monthly intravenous (IV) infusion

Experimental: High Dose - Monthly intravenous (IV) infusion


Treatment: Drugs: Aducanumab (BIIB037)
Low dose

Treatment: Drugs: Aducanumab (BIIB037)
High dose

Treatment: Drugs: Placebo
Placebo
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change From Baseline in Clinical Dementia Rating Sum of Boxes (CDR-SB) Score at Week 78
Timepoint [1] 0 0
Baseline, Week 78
Secondary outcome [1] 0 0
Change From Baseline in Mini-Mental State Examination (MMSE) Score at Week 78
Timepoint [1] 0 0
Baseline, Week 78
Secondary outcome [2] 0 0
Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale (13 Items) (ADAS-Cog 13) Score at Week 78
Timepoint [2] 0 0
Baseline, Week 78
Secondary outcome [3] 0 0
Change From Baseline in Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory (Mild Cognitive Impairment Version) (ADCS-ADL-MCI) Score at Week 78
Timepoint [3] 0 0
Baseline, Week 78

Eligibility
Key inclusion criteria
Key

* Must meet all of the following clinical criteria for MCI due to AD or mild AD and must have:
* A Clinical Dementia Rating (CDR)-Global Score of 0.5.
* Objective evidence of cognitive impairment at screening
* An MMSE score between 24 and 30 (inclusive)
* Must have a positive amyloid Positron Emission Tomography (PET) scan
* Must consent to apolipoprotein E (ApoE) genotyping
* If using drugs to treat symptoms related to AD, doses must be stable for at least 8 weeks prior to screening visit 1
* Must have a reliable informant or caregiver

Key
Minimum age
50 Years
Maximum age
85 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Any medical or neurological condition (other than Alzheimer's Disease) that might be a contributing cause of the subject's cognitive impairment
* Have had a stroke or Transient Ischemic Attack (TIA) or unexplained loss of consciousness in the past 1 year
* Clinically significant unstable psychiatric illness in past 6 months
* History of unstable angina, myocardial infarction, advanced chronic heart failure, or clinically significant conduction abnormalities within 1 year prior to Screening
* Indication of impaired renal or liver function
* Have human immunodeficiency virus (HIV) infection
* Have a significant systematic illness or infection in past 30 days
* Relevant brain hemorrhage, bleeding disorder and cerebrovascular abnormalities
* Any contraindications to brain magnetic resonance imaging (MRI) or PET scans
* Alcohol or substance abuse in past 1 year
* Taking blood thinners (except for aspirin at a prophylactic dose or less)

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
13/08/2015
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
8/08/2019
Sample size
Target
Accrual to date
Final
1653
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC,WA
Recruitment hospital [1] 0 0
St Vincent's Hospital Sydney - Darlinghurst
Recruitment hospital [2] 0 0
Central Coast Neurosciences Research, Gosford - East Gosford
Recruitment hospital [3] 0 0
Central Coast Neurosciences Research - Erina
Recruitment hospital [4] 0 0
KARA Institute for Neurological Diseases - North Ryde
Recruitment hospital [5] 0 0
Calvary Mater Newcastle - Waratah
Recruitment hospital [6] 0 0
The Prince Charles Hospital - Chermside
Recruitment hospital [7] 0 0
Royal Brisbane and Women's Hospital - Herston
Recruitment hospital [8] 0 0
Toowoomba Base Hospital - Toowoomba
Recruitment hospital [9] 0 0
Box Hill Hospital - Box Hill
Recruitment hospital [10] 0 0
Austin Hospital - Heidelberg
Recruitment hospital [11] 0 0
Royal Melbourne Hospital - Parkville
Recruitment hospital [12] 0 0
Neurodegenerative Disorders Research - West Perth
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
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2250 - East Gosford
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2250 - Erina
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2113 - North Ryde
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2298 - Waratah
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4032 - Chermside
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4006 - Herston
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4350 - Toowoomba
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3128 - Box Hill
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3084 - Heidelberg
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3050 - Parkville
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6005 - West Perth
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Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Biogen
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The primary objective of the study is to evaluate the efficacy of monthly doses of aducanumab in slowing cognitive and functional impairment as measured by changes in the Clinical Dementia Rating-Sum of Boxes (CDR-SB) score as compared with placebo in participants with early AD. Secondary objectives are to assess the effect of monthly doses of aducanumab as compared with placebo on clinical progression as measured by Mini-Mental State Examination (MMSE), AD Assessment Scale-Cognitive Subscale (13 items) \[ADAS-Cog 13\], and AD Cooperative Study-Activities of Daily Living Inventory (Mild Cognitive Impairment version) \[ADCS-ADL-MCI\].
Trial website
https://clinicaltrials.gov/study/NCT02477800
Trial related presentations / publications
Salloway S, Chalkias S, Barkhof F, Burkett P, Barakos J, Purcell D, Suhy J, Forrestal F, Tian Y, Umans K, Wang G, Singhal P, Budd Haeberlein S, Smirnakis K. Amyloid-Related Imaging Abnormalities in 2 Phase 3 Studies Evaluating Aducanumab in Patients With Early Alzheimer Disease. JAMA Neurol. 2022 Jan 1;79(1):13-21. doi: 10.1001/jamaneurol.2021.4161.
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Biogen
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT02477800